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Am J Physiol Renal Physiol (December 12, 2007). doi:10.1152/ajprenal.00500.2007
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Submitted on October 24, 2007
Accepted on December 11, 2007

Melatonin ameliorates oxidative stress, inflammation, proteinuria and progression of renal damage in rats with renal mass reduction

Yasmir Quiroz1, Atilio Ferrebuz1, Freddy Romero1, Nosratola D. Vaziri2, and Bernardo Rodriguez-Iturbe3*

1 Centro de Investigaciones Biomedicas, IVIC-Zulia, Maracaibo, ZULIA, Venezuela
2 Department of Medicine, Division of Nephrology & Hypertension, University of California Irvine Medical Center, Orange, California, United States
3 Nefrologia, Centro de Medicina Experimental, Hospital Universitario, Universidad del Zulia, Venezuela; Centro de Investigaciones Biomedicas, IVIC-Zulia, Maracaibo, ZULIA, Venezuela

* To whom correspondence should be addressed. E-mail: bernardori{at}telcel.net.ve.

The progressive deterioration of renal function and structure resulting from renal mass reduction are mediated by a variety of mechanisms, including oxidative stress and inflammation. Melatonin, the major product of the pineal gland, has potent antioxidant and anti-inflammatory properties and its production is impaired in chronic renal failure. We therefore investigated if melatonin treatment would modify the course of chronic renal failure in the remnant kidney model. We studied rats followed 12 weeks after renal ablation untreated (Nx group, n=7) and treated with melatonin administered in the drinking water (10 mg/100ml) (Nx+MEL group, n=8). Sham-operated rats (n=10) were used as controls. Melatonin administration increased 13-15 times the endogenous hormone levels. Rats in the Nx+MEL group had reduced oxidative stress (malondialdehyde levels in plasma and in the remnant kidney as well as nitrotyrosine renal abundance) and renal inflammation (p65 NF{kappa}B positive renal interstitial cells and infiltration of lymphocytes and macrophages). Collagen, {alpha}-SMA, and TGF-{beta} renal abundance were all increased in the remnant kidney of the untreated rats and were reduced significantly by melatonin treatment. Deterioration of renal function (plasma creatinine and proteinuria) and structure (glomerulosclerosis and tubulointerstitial damage) resulting from renal ablation were ameliorated significantly with melatonin treatment. In conclusion, melatonin administration improves the course of chronic renal failure in rats with renal mass reduction. Further studies are necessary to define the potential usefulness of this treatment in other animal models and in patients with chronic renal disease.




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